Lorena Varela‐Nallar

ORCID: 0000-0003-2588-6437
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About
Contact & Profiles
Research Areas
  • Neurogenesis and neuroplasticity mechanisms
  • Genetics and Neurodevelopmental Disorders
  • Wnt/β-catenin signaling in development and cancer
  • Alzheimer's disease research and treatments
  • Neuroscience and Neuropharmacology Research
  • Axon Guidance and Neuronal Signaling
  • Trace Elements in Health
  • Prion Diseases and Protein Misfolding
  • Neurological diseases and metabolism
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Reproductive System and Pregnancy
  • Epigenetics and DNA Methylation
  • Biochemical effects in animals
  • Cancer-related gene regulation
  • Nuclear Receptors and Signaling
  • Endoplasmic Reticulum Stress and Disease
  • Adenosine and Purinergic Signaling
  • Retinoids in leukemia and cellular processes
  • Air Quality and Health Impacts
  • Anesthesia and Neurotoxicity Research
  • Reproductive tract infections research
  • Genetic Syndromes and Imprinting
  • Genetic and Kidney Cyst Diseases
  • Parathyroid Disorders and Treatments
  • Ginkgo biloba and Cashew Applications

Universidad Andrés Bello
2015-2025

Institute of Biomedical Science
2023-2024

Millennium Engineering and Integration (United States)
2024

Pontificia Universidad Católica de Chile
2002-2015

Universidad de Santiago de Chile
2000-2010

Growing evidence indicates that Wingless-type (Wnt) signaling plays an important role in the maturation of central nervous system. We report here family member 5A (Wnt-5a) is expressed early development and stimulates dendrite spine morphogenesis, inducing de novo formation spines increasing size preexisting ones hippocampal neurons. Wnt-5a increased intracellular calcium concentration dendritic processes amplitude NMDA spontaneous miniature currents. Acute application field excitatory...

10.1073/pnas.1010011107 article EN Proceedings of the National Academy of Sciences 2010-11-17

In the adult brain new neurons are continuously generated mainly in two regions, subventricular zone (SVZ) of lateral ventricles and subgranular (SGZ) hippocampal dentate gyrus. SGZ, radial neural stem cells (NSCs) give rise to granule that integrate into circuitry relevant for plasticity hippocampus. Loss neurogenesis impairs learning memory, suggesting this process is important function. Adult tightly regulated by multiple signaling pathways, including canonical Wnt/β-catenin pathway. This...

10.3389/fncel.2013.00100 article EN cc-by Frontiers in Cellular Neuroscience 2013-01-01

The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic that clusters glutamate receptors and is critical plasticity. PSD95 levels are diminished in ageing neurodegenerative disorders, including Alzheimer's disease Huntington's disease. epigenetic mechanisms (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, largely unknown, limiting the development targeted epigenome therapy. We analysed Dlg4/PSD95 landscape hippocampal tissue designed...

10.1093/brain/awx272 article EN Brain 2017-10-05

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive abilities, the appearance amyloid plaques composed amyloid-β peptide (Aβ) neurofibrillary tangles formed tau protein. It has been suggested that exercise might ameliorate disease; here, we evaluated effect voluntary running on several aspects AD including deposition, phosphorylation, inflammatory reaction, neurogenesis spatial in double transgenic APPswe/PS1ΔE9 mouse model AD. We report...

10.1111/bpa.12255 article EN Brain Pathology 2015-03-11

Abstract In the adult hippocampus, new neurons are generated in dentate gyrus. The Wnt signaling pathway regulates this process, but little is known about endogenous ligands involved. We investigated role of Wnt5a on hippocampal neurogenesis. neuronal morphogenesis during embryonic development, and maintains dendritic architecture pyramidal hippocampus. Here, we determined that knockdown mouse gyrus by lentivirus-mediated shRNA impaired differentiation progenitor cells, reduced development...

10.1002/stem.3121 article EN Stem Cells 2019-11-13

Abstract Background The Wnt signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation plasticity. Some components are localized at central synapses, it is thus possible that this could activated the synapse. Results We examined distribution receptor Frizzled-1 cultured hippocampal neurons determined located contacts co-localizing with presynaptic proteins. was found functional synapses...

10.1186/1749-8104-4-41 article EN cc-by Neural Development 2009-11-02

In the adult hippocampus new neurons are continuously generated from neural stem cells (NSCs) present at subgranular zone of dentate gyrus. This process is controlled by Wnt signaling, which plays a complex role in regulating multiple steps neurogenesis including maintenance, proliferation and differentiation progenitor development newborn neurons. Differential effects signaling during progression could be mediated cell-type specific expression receptors. Here we studied potential Frizzled-1...

10.1186/s13041-016-0209-3 article EN cc-by Molecular Brain 2016-03-15

Hypoxia modulates proliferation and differentiation of cultured embryonic adult stem cells, an effect that includes β-catenin, a key component the canonical Wnt signaling pathway. Here we studied mild hypoxia on activity Wnt/β-catenin pathway in hippocampus mice vivo. The hypoxia-inducible transcription factor-1α (HIF-1α) was analyzed as molecular control physiological hypoxic response. Exposure to chronic (10% oxygen for 6-72 h) stimulated activation Because is positive modulator...

10.3389/fncel.2014.00017 article EN cc-by Frontiers in Cellular Neuroscience 2014-01-01

Astrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into neighboring synapses, which can modulate synaptic activity and are necessary for fear memory consolidation. However, the released, their mechanisms of action remain elusive. Here, we report that conditioning training elevated Cx43 hemichannel in astrocytes from basolateral amygdala (BLA). The selective blockade by microinfusion TAT-Cx43L2 peptide BLA induced deficits 1 24 h after training, without affecting...

10.1096/fj.202100798rr article EN The FASEB Journal 2022-01-21

Abstract The activation of the canonical Wnt signaling pathway protects hippocampal neurons against toxicity Alzheimer's amyloid‐β‐peptide (Aβ), however, role played by receptors Frizzleds, has not been studied. We report here that Frizzled‐1 mediates Wnt/β‐catenin Wnt3a in PC12 cells. In addition, protective effect Aβ oligomers was modulated expression levels both cells and neurons. Over‐expression significantly increased cell survival induced diminished caspase‐3 activation, while...

10.1002/jcp.21497 article EN Journal of Cellular Physiology 2008-06-02

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) plays a key role in the regulation of calcium-dependent gene expression. The expression CaMKIV and activation CREB regulated genes are involved memory neuronal survival. We report here that: (a) bioinformatic analysis 15,476 promoters human genome predicted several Wnt target genes, being very interesting candidate; (b) promoter contains TCF/LEF transcription motifs similar to those present genes; (c) biochemical studies indicate that...

10.1002/jcp.21902 article EN Journal of Cellular Physiology 2009-08-27

Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons linked differentiation neuroprotection. In the present study, role of SIRT1 dendritic development was evaluated cultured hippocampal were transfected at 3 days vitro with construct coding or dominant negative SIRT1H363Y, lacks catalytic activity. Neurons overexpressing showed an increased arborization, while SIRT1H363Y...

10.1371/journal.pone.0047073 article EN cc-by PLoS ONE 2012-10-04

Considerable evidence indicates that the NMDA receptor (NMDAR) subunits NR2A and NR2B are critical mediators of synaptic plasticity dendritogenesis; however, how they differentially regulate these processes is unclear. Here we investigate roles subunits, their scaffolding proteins PSD-95 SAP102, in remodeling dendritic architecture developing hippocampal neurons (2–25 DIV). Analysis temporal spatial expression patterns NMDARs anchoring immature cultures revealed a strong positive correlation...

10.1371/journal.pone.0094037 article EN cc-by PLoS ONE 2014-04-04

Andrographolide (ANDRO) is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO competitive inhibitor glycogen synthase kinase-3 β (GSK-3 ), key enzyme the Wnt/ -catenin signaling cascade. Since this pathway regulates neurogenesis in adult hippocampus, we evaluated whether stimulates process. Treatment with increased neural progenitor cell proliferation and number immature neurons hippocampus 2-...

10.1155/2015/935403 article EN cc-by Neural Plasticity 2015-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ) accumulation and synaptic alterations. Previous studies indicated that hyperforin, component the St John's Wort, prevents Aβ neurotoxicity some behavioral impairments in rat model AD. In this study we examined ability tetrahydrohyperforin (IDN5607), stable hyperforin derivative, to prevent deficit impairment an vivo double transgenic...

10.1038/tp.2011.19 article EN cc-by Translational Psychiatry 2011-07-12
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